Project Summary Male infertility and subfertility accounts for roughly half of the 10-15% prevalence of overall failure to conceive a child. An accumulated body of evidence across the past two decades suggests fetal origins of adult male reproductive dysfunction. Male reproductive dysfunction could proceed inter- generationally, with parental work contributing to male subfertility in the next generation, and increased vulnerability to second insult in the adult male exposed in utero or via parental occupation. We will use data on male reproductive parameters, occupational data, and relevant covariates collected by the Study for Future Families (SFF) to examine the role of occupational contributions to depression of male fertility indices including semen quality parameters, male hormonal levels, and testicular size measurements. Occupational exposure indices will include reported occupation, specific job exposures reported in the SFF, and a job-exposure matrix describing exposure to endocrine-disrupting chemicals. Additionally, using a unique set of maternal questionnaire data on occupational exposures, we will assess intergenerational influences on men's reproductive indices by modeling direct and mediated effects of both parental and male-partner occupational exposures on male fertility profiles. This will assess male vulnerability (arising from parental occupational exposure) to a second insult to reproductive capacity. This proposal is one of the first to examine the role of occupational exposures sustained by parents of male subjects in reduced fertility or susceptibility to insult from occupational exposures in the subsequent generation. The richness of this dataset, combined with the linkage of male fertility parameters with parental occupational data, is an opportunity to test of a novel hypothesis on intergenerational transmission of male subfecudity. The findings of this proposed study will lay the groundwork for efforts to reduce potentially hazardous occupational exposures in both fertile men and women across generations. This proposal addresses the NORA cross-sector program in Cancer, Reproductive and Cardiovascular Diseases which, with other CDC partners, aims to better identify and control reproductive toxicant exposures, and is relevant to the health of workers in the Healthcare, Manufacturing, and Construction NORA sectors. As the NIOSH Program Portfolio notes, the overall contribution of occupational exposures to male and female infertility remains unknown; this effort will make a significant contribution toward a research agenda on male and intergenerational workplace exposures and fertility. The work supports NIOSH r2p initiatives in providing detailed information on adverse reproductive exposures in the workplace, and their mitigation, as well as increasing protection of workers who may be at greater risk from prior parental exposures.